tbuckley/cabot-search huggingface dataset:
Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial
Authors: Kohei Shitara, Florian Lordick, Yung-Jue Bang, Peter Enzinger, David Ilson, Manish A Shah, Eric Van Cutsem, Rui-Hua Xu, Giuseppe Aprile, Jianming Xu, Joseph Chao, Roberto Pazo-Cid, Yoon-Koo Kang, Jianning Yang, Diarmuid Moran, Pranob Bhattacharya, Ahsan Arozullah, Jung Wook Park, Mok Oh, Jaffer A Ajani
Journal: The Lancet (2023)
Trial of thromboxane receptor inhibition with ifetroban: TP receptors regulate eicosanoid homeostasis in aspirin-exacerbated respiratory disease
Authors: Tanya M. Laidlaw, Kathleen M. Buchheit, Katherine N. Cahill, Jonathan Hacker, Laura Cho, Jing Cui, Chunli Feng, Chongjia C. Chen, Meghan Le, Elliot Israel, Joshua A. Boyce
Journal: Journal of Allergy and Clinical Immunology (2023)
Symptoms and Satisfaction Levels Associated with Intraocular Lens Implants in the Monofocal and Premium IOL Patient-Reported Outcome Measure Study
Authors: Samuel Masket, Flora Lum, Scott MacRae, Ron D. Hays, Michelle E. Tarver, Jack Holladay, Geunyoung Yoon, Tieuvi Nguyen, Walter Stark, Nisha Kumar, George Lau, Steven Schallhorn, Malvina Eydelman
Journal: Ophthalmology (2023)
Natural killer cell-mimic nanoparticles can actively target and kill acute myeloid leukemia cells
Authors: Hojjat Alizadeh Zeinabad, Wen Jie Yeoh, Maryam Arif, Mihai Lomora, Yara Banz, Carsten Riether, Philippe Krebs, Eva Szegezdi
Journal: Biomaterials (2023)

Natural killer (NK) cells play a crucial role in recognizing and killing emerging tumor cells. However, tumor cells develop mechanisms to inactivate NK cells or hide from them. Here, we engineered a modular nanoplatform that acts as NK cells (NK cell-mimics), carrying the tumor-recognition and death ligand-mediated tumor-killing properties of an NK cell, yet without being subject to tumor-mediated inactivation. NK cell mimic nanoparticles (NK.NPs) incorporate two key features of activated NK cells: cytotoxic activity via the death ligand, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and an adjustable tumor cell recognition feature based on functionalization with the NK cell Fc-binding receptor (CD16, FCGR3A) peptide, enabling the NK.NPs to bind antibodies targeting tumor antigens. NK.NPs showed potent in vitro cytotoxicity against a broad panel of cancer cell lines. Upon functionalizing the NK.NPs with an anti-CD38 antibody (Daratumumab), NK.NPs effectively targeted and eliminated CD38-positive patient-derived acute myeloid leukemia (AML) blasts ex vivo and were able to target and kill CD38-positive AML cells in vivo, in a disseminated AML xenograft system and reduced AML burden in the bone marrow compared to non-targeted, TRAIL-functionalized liposomes. Taken together, NK.NPs are able to mimicking key antitumorigenic functions of NK cells and warrant their development into nano-immunotherapeutic tools.
The Dutch Working Party on Antibiotic Policy (SWAB) guideline for the approach to suspected antibiotic allergy
Authors: Roos Wijnakker, Maurits S. van Maaren, Lonneke G.M. Bode, Maja Bulatovic, Bart J.C. Hendriks, Masja C.M. Loogman, Suzanne P.M. Lutgens, Ananja Middel, Chris M.G. Nieuwhof, Eveline E. Roelofsen, Jan W. Schoones, Kim C.E. Sigaloff, Aline B. Sprikkelman, Lieke M.M. de Vrankrijker, Mark G.J. de Boer
Journal: Clinical Microbiology and Infection (2023)
Integrating tuberculosis and COVID-19 molecular testing in Lima, Peru: a cross-sectional, diagnostic accuracy study
Authors: Emily Lai-Ho MacLean, Luz Villa-Castillo, Patricia Espinoza-Lopez, Tatiana Caceres, Giorgia Sulis, Mikashmi Kohli, Madhukar Pai, César Ugarte-Gil
Journal: The Lancet Microbe (2023)

BackgroundIntegrated molecular testing could be an opportunity to detect and provide care for both tuberculosis and COVID-19. Many high tuberculosis burden countries, such as Peru, have existing GeneXpert systems for tuberculosis testing with GeneXpert Xpert MTB/RIF Ultra (Xpert Ultra), and a GeneXpert SARS-CoV-2 assay, GeneXpert Xpert Xpress SARS-CoV-2 (Xpert Xpress), is also available. We aimed to assess the feasibility of integrating tuberculosis and COVID-19 testing using one sputum specimen with Xpert Ultra and Xpert Xpress in Lima, Peru.MethodsIn this cross-sectional, diagnostic accuracy study, we recruited adults presenting with clinical symptoms or suggestive history of tuberculosis or COVID-19, or both. Participants were recruited from a total of 35 primary health facilities in Lima, Peru. Participants provided one nasopharyngeal swab and one sputum sample. For COVID-19, we tested nasopharyngeal swabs and sputum using Xpert Xpress; for tuberculosis, we tested sputum using culture and Xpert Ultra. We compared diagnostic accuracy of sputum testing using Xpert Xpress with nasopharyngeal swab testing using Xpert Xpress. Individuals with positive Xpert Xpress nasopharyngeal swab results were considered COVID-19 positive, and a positive culture indicated tuberculosis. To assess testing integration, the proportion of cases identified in sputum by Xpert Xpress was compared with Xpert Xpress on nasopharyngeal swabs, and sputum by Xpert Ultra was compared with culture.FindingsBetween Jan 11, 2021, and April 26, 2022, we recruited 600 participants (312 [52%] women and 288 [48%] men). In-study prevalence of tuberculosis was 13% (80 participants, 95% CI 11–16) and of SARS-CoV-2 was 35% (212 participants, 32–39). Among tuberculosis cases, 13 (2·2%, 1·2–3·7) participants were concurrently positive for SARS-CoV-2. Regarding the diagnostic yield of integrated testing, Xpert Ultra detected 96% (89–99) of culture-confirmed tuberculosis cases (n=77), and Xpert Xpress-sputum detected 67% (60–73) of COVID-19 cases (n=134). All five study staff reported that integrated molecular testing was easy and acceptable.InterpretationThe diagnostic yield of Xpert Xpress on sputum was moderate, but integrated testing for tuberculosis and COVID-19 with GeneXpert was feasible. However, systematic testing for both diseases might not be the ideal approach for everyone presenting with presumptive tuberculosis or COVID-19, as concurrent positive cases were rare during the study period. Further research might help to identify when integrated testing is most worthwhile and its optimal implementation.FundingCanadian Institutes of Health Research and International Development Research Centre.TranslationFor the Spanish translation of the abstract see Supplementary Materials section.
Mainstreaming Wastewater Surveillance for Infectious Disease
Authors: Michelle M. Mello, John S. Meschke, Guy H. Palmer
Journal: New England Journal of Medicine (2023)

Interview with Profs. Michelle Mello and Guy Palmer on wastewater surveillance during the Covid-19 pandemic and beyond. (14:19)Download A National Academies committee recently assessed the value of community-level wastewater surveillance in controlling infectious diseases beyond Covid-19. What are the key challenges in achieving that vision?
The role of Chlamydiales in adverse pregnancy outcome: a community-based nested case-control study
Authors: Axel Skafte-Holm, Thomas Roland Pedersen, Anna Sandager, Rikke Damkjær Maimburg, Camilla Lindahl, Niels Uldbjerg, Jørgen Skov Jensen
Journal: Clinical Microbiology and Infection (2023)

Over the last decades, the Chlamydiales order has expanded and a new group of Chlamydia-related bacteria has emerged, covering species such as Waddlia chondrophila associated with bovine abortion. However, it is unknown whether they compromise human reproduction such as Chlamydia trachomatis. We therefore aimed to investigate the association between vaginal colonization of selected species of the Chlamydiales order with spontaneous abortion, preterm birth, and animal exposure.Pregnant women were enrolled at the nuchal translucency scan or when admitted for suspected miscarriage at Aarhus University Hospital, Denmark. Cases were defined as spontaneous abortion <22 weeks and preterm birth <37 weeks. Controls were defined as term birth ≥37 weeks. Vaginal samples from 1203 women were assessed using C. trachomatis, W. chondrophila, and pan-Chlamydiales-specific real-time PCRs targeting the 16S rRNA gene.A total of 1120 women of primarily Caucasian ancestry were enrolled, including 193 spontaneous abortions, 88 preterm births, and 839 term births. After sequencing for verification, the prevalence of Chlamydiales was 3 of 193 (1.6%; 95% CI, 0.5-4.8) in women experiencing spontaneous abortion, 2 of 88 (2.3%; 95% CI, 0.6-8.9) in women with preterm birth, and 20 of 839 (2.4%; 95% CI, 1.6-3.7) in women giving birth at term. Thus, Chlamydiales infection was neither significantly associated with spontaneous abortion (OR, 0.68; 95% CI, 0.15-2.01) nor preterm birth (OR, 1.02; 95% CI, 0.15-3.60) compared with women giving birth at term. Amplicons from the pan-Chlamydiales assay revealed close sequence homology and were primarily identified as uncultured Chlamydiales bacteria.Among Danish pregnant women, the prevalence of Chlamydiales was low and not associated with adverse pregnancy outcomes.
HIV treatment-as-prevention and its effect on incidence of HIV among cisgender gay, bisexual, and other men who have sex with men in Australia: a 10-year longitudinal cohort study
Authors: Denton Callander, Hamish McManus, Richard T Gray, Andrew E Grulich, Andrew Carr, Jennifer Hoy, Basil Donovan, Christopher K Fairley, Martin Holt, David J Templeton, Siaw-Teng Liaw, James H McMahon, Jason Asselin, Kathy Petoumenos, Margaret Hellard, Alisa Pedrana, Julian Elliott, Phillip Keen, Jane Costello, Richard Keane, John Kaldor, Mark Stoové, Rebecca Guy
Journal: The Lancet HIV (2023)
Medications affecting the insulin-like growth factor 1/growth hormone axis, including teprotumumab, somatostatin analogs, and anti-calcitonin gene-related peptide monoclonal antibodies, are associated with elevated reporting odds of alopecia in women: A pharmacovigilance study
Authors: Patrick Michael Jedlowski, Mahdieh F. Jedlowski, Mohammad Fazel
Journal: Journal of the American Academy of Dermatology (2023)
The structure and function of YTHDF epitranscriptomic m6A readers
Authors: Vilbert Sikorski, Simona Selberg, Maciej Lalowski, Mati Karelson, Esko Kankuri
Journal: Trends in Pharmacological Sciences (2023)

Specific RNA sequences modified by a methylated adenosine, N6-methyladenosine (m6A), contribute to the post-transcriptional regulation of gene expression. The quantity of m6A in RNA is orchestrated by enzymes that write and erase it, while its effects are mediated by proteins that bind to read this modification. Dysfunction of this post-transcriptional regulatory process has been linked to human disease. Although the initial focus has been on pharmacological targeting of the writer and eraser enzymes, interest in the reader proteins has been challenged by a lack of clear understanding of their functional roles and molecular mechanisms of action. Readers of m6A-modified RNA (m6A-RNA) – the YTH (YT521-B homology) domain-containing protein family paralogs 1–3 (YTHDF1–3, referred to here as DF1–DF3) – are emerging as therapeutic targets as their links to pathological processes such as cancer and inflammation and their roles in regulating m6A-RNA fate become clear. We provide an updated understanding of the modes of action of DF1–DF3 and review their structures to unlock insights into drug design approaches for DF paralog-selective inhibition.
The Principles of Ante-Natal and Post-Natal Child Hygiene.
Authors: W. M. Feldman
Journal: JAMA (1928)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Effects of Atrial Fibrillation Screening According to N-Terminal Pro-B-Type Natriuretic Peptide: A Secondary Analysis of the Randomized LOOP Study
Authors: Lucas Yixi Xing, Søren Zöga Diederichsen, Søren Højberg, Derk W. Krieger, Claus Graff, Ruth Frikke-Schmidt, Morten S. Olesen, Axel Brandes, Lars Køber, Ketil Jørgen Haugan, Jesper Hastrup Svendsen
Journal: Circulation (2023)

Research suggests NT-proBNP (N-terminal pro-B-type natriuretic peptide) to be a strong predictor of incident atrial fibrillation (AF) and stroke. However, its utility in AF screening remains unknown. The aim of this study was to investigate NT-proBNP as a potential marker for screening efficacy with respect to AF yield and stroke prevention.
People With Type 1 Diabetes of African Caribbean Ethnicity Are at Increased Risk of Developing Sight-Threatening Diabetic Retinopathy
Authors: Anastasios Mangelis, Piyumi Wijewickrama, Abbeyramei Nirmalakumaran, Nikolaos Fountoulakis, Prashanth Vas, Laura Webster, Samantha Mann, Julian Collins, David Hopkins, Stephen Thomas, Salma Ayis, Janaka Karalliedde
Journal: Diabetes Care (2023)

OBJECTIVE There is limited information on the effect of ethnicity on the development of referable sight-threatening diabetic retinopathy (STDR) in people with type 1 diabetes. This study describes the risk factors for STDR in a diverse cohort of people with type 1 diabetes attending a regional diabetes eye screening service. RESEARCH DESIGN AND METHODS Clinical and digital retinal imaging data from 1,876 people with type 1 diabetes (50% women, 72.1% Caucasian, 17.3% African Caribbean, 2.9% Asian, and 7.6% other) with no retinopathy at baseline, attending surveillance eye screening were reviewed. Referable STDR was defined as the presence of any moderate to severe nonproliferative or preproliferative diabetic retinopathy or proliferative diabetic retinopathy or maculopathy in either eye as per U.K. National Diabetic Eye Screening criteria. Median follow-up was 6 years. RESULTS The median (interquartile range) age of the cohort was 29 (21, 41) years. Of the cohort of 1,876 people, 359 (19%) developed STDR. People who developed STDR had higher baseline HbA1c, raised systolic blood pressure (SBP), longer diabetes duration, and were more often of African Caribbean origin (24% vs. 15.6%; P &amp;lt; 0.05 for all). In multivariable Cox regression analyses, African Caribbean ethnicity (hazard ratio [HR] 1.39, 95% CI 1.09–1.78, P = 0.009), baseline SBP (HR 1.01, 95% CI 1.00–1.01, P = 0.033), and baseline HbA1c (HR 1.01, 95% CI 1.00–1.01, P = 0.0001) emerged as independent risk factors for STDR. CONCLUSIONS We observed that people with type 1 diabetes of African Caribbean ethnicity are at significantly greater risk of STDR. Further research is required to understand the mechanisms that explain this novel observation.
Spatiotemporal tracking of gold nanorods after intranasal administration for brain targeting
Authors: Shunping Han, Julie Tzu-Wen Wang, Emine Yavuz, Alaa Zam, Nadia Rouatbi, Rifka Nurul Utami, Revadee Liam-Or, Alexander Griffiths, Wayne Dickson, Jane Sosabowski, Khuloud T. Al-Jamal
Journal: Journal of Controlled Release (2023)

Intranasal administration is becoming increasingly more attractive as a fast delivery route to the brain for therapeutics circumventing the blood-brain barrier (BBB). Gold nanorods (AuNRs) demonstrate unique optical and biological properties compared to other gold nanostructures due to their high aspect ratio. In this study, we investigated for the first time the brain region-specific distribution of AuNRs and their potential as a drug delivery platform for central nervous system (CNS) therapy following intranasal administration to mice using a battery of analytical and imaging techniques. AuNRs were functionalized with a fluorescent dye (Cyanine5, Cy5) or a metal chelator (diethylenetriaminepentaacetic dianhydride, DTPA anhydride) to complex with Indium-111 via a PEG spacer for optical and nuclear imaging, respectively. Direct quantification of gold was achieved by inductively coupled plasma mass spectrometry. Rapid AuNRs uptake in mice brains was observed within 10 min following intranasal administration which gradually reduced over time. This was confirmed by the 3 imaging/analytical techniques. Autoradiography of sagittal brain sections suggested entry to the brain via the olfactory bulb followed by diffusion to other brain regions within 1 h of administration. The presence of AuNR in glioblastoma (GBM) tumors following intranasal administration was also proven which opens doors for AuNRs applications, as nose-to-brain drug delivery carriers, for treatment of a range of CNS diseases.
Metabolic Reprogramming Driven by IGF2BP3 Promotes Acquired Resistance to EGFR Inhibitors in Non–Small Cell Lung Cancer
Authors: Ziyou Lin, Jingwei Li, Jian Zhang, Weineng Feng, Jiaye Lu, Xiaofan Ma, Wen Ding, Shumin Ouyang, Jinjian Lu, Peibin Yue, Guohui Wan, Peiqing Liu, Xiaolei Zhang
Journal: Cancer Research (2023)

Abstract Acquired resistance represents a bottleneck for effective molecular targeted therapy in lung cancer. Metabolic adaptation is a distinct hallmark of human lung cancer that might contribute to acquired resistance. In this study, we discovered a novel mechanism of acquired resistance to EGFR tyrosine kinase inhibitors (TKI) mediated by IGF2BP3-dependent cross-talk between epigenetic modifications and metabolic reprogramming through the IGF2BP3–COX6B2 axis. IGF2BP3 was upregulated in patients with TKI-resistant non–small cell lung cancer, and high IGF2BP3 expression correlated with reduced overall survival. Upregulated expression of the RNA binding protein IGF2BP3 in lung cancer cells reduced sensitivity to TKI treatment and exacerbated the development of drug resistance via promoting oxidative phosphorylation (OXPHOS). COX6B2 mRNA bound IGF2BP3, and COX6B2 was required for increased OXPHOS and acquired EGFR-TKI resistance mediated by IGF2BP3. Mechanistically, IGF2BP3 bound to the 3′-untranslated region of COX6B2 in an m6A-dependent manner to increase COX6B2 mRNA stability. Moreover, the IGF2BP3–COX6B2 axis regulated nicotinamide metabolism, which can alter OXPHOS and promote EGFR-TKI acquired resistance. Inhibition of OXPHOS with IACS-010759, a small-molecule inhibitor, resulted in strong growth suppression in vitro and in vivo in a gefitinib-resistant patient-derived xenograft model. Collectively, these findings suggest that metabolic reprogramming by the IGF2BP3–COX6B2 axis plays a critical role in TKI resistance and confers a targetable metabolic vulnerability to overcome acquired resistance to EGFR-TKIs in lung cancer. Significance: IGF2BP3 stabilizes COX6B2 to increase oxidative phosphorylation and to drive resistance to EGFR inhibitors in lung cancer, which provides a therapeutic strategy to overcome acquired resistance by targeting metabolic transitions.
Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation and Progression
Authors: Janine M. DeBlasi, Aimee Falzone, Samantha Caldwell, Nicolas Prieto-Farigua, Justin R. Prigge, Edward E. Schmidt, Iok In Christine Chio, Florian A. Karreth, Gina M. DeNicola
Journal: Cancer Research (2023)

Mutations in the KEAP1-NRF2 (Kelch-like ECH-associated protein 1-nuclear factor-erythroid 2 p45-related factor 2) pathway occur in up to a third of non-small cell lung cancer (NSCLC) cases and often confer resistance to therapy and poor outcomes. Here, we developed murine alleles of the KEAP1 and NRF2 mutations found in human NSCLC and comprehensively interrogated their impact on tumor initiation and progression. Chronic NRF2 stabilization by Keap1 or Nrf2 mutation was not sufficient to induce tumorigenesis, even in the absence of tumor suppressors, p53 or LKB1. When combined with KrasG12D/+, constitutive NRF2 activation promoted lung tumor initiation and early progression of hyperplasia to low-grade tumors but impaired their progression to advanced-grade tumors, which was reversed by NRF2 deletion. Finally, NRF2 overexpression in KEAP1 mutant human NSCLC cell lines was detrimental to cell proliferation, viability, and anchorage-independent colony formation. Collectively, these results establish the context-dependence and activity threshold for NRF2 during the lung tumorigenic process.
Tumor-Agnostic Precision Medicine from the AACR GENIE Database: Clinical Implications
Authors: Mohamed A. Gouda, Blessie E. Nelson, Lars Buschhorn, Adam Wahida, Vivek Subbiah
Journal: Clinical Cancer Research (2023)

Biomarker-driven cancer therapy has revolutionized precision oncology. With a better understanding of tumor biology, tissue-agnostic targets have been characterized and explored, which ultimately led to therapeutics with pan-cancer efficacy. To date, five molecular biomarkers have obtained FDA tissue-agnostic approval for targeted therapies and immunotherapies. Those include BRAFV600E mutations, RET fusions, NTRK fusions, high tumor mutation burden (TMB), and deficient mismatch repair/high microsatellite instability (dMMR/MSI-High). Herein, we have used data from AACR project GENIE to explore the clinico-genomic landscape of these alterations. AACR GENIE is a publicly accessible registry of genomic data from multiple collaborating cancer centers. Current database (version 13.0) includes sequencing data of 168,423 samples collected from patients with different cancers. We were able to identify BRAFV600E, RET fusions, NTRK fusions, and high TMB in 2.9%, 1.6%, 1.5%, and 15.2% of pan-cancer samples, respectively. In this article, we describe the distribution of those tissue-agnostic targets among different cancer types. In addition, we summarize the current prospect on the biology of these alterations and evidence on approved drugs, including pembrolizumab, dostarilmab, larotrectinib, entrectinib, selpercatinib, and dabrafenib/trametinib combination.
Pyruvate-supported flux through medium-chain ketothiolase promotes mitochondrial lipid tolerance in cardiac and skeletal muscles
Authors: Timothy R. Koves, Guo-Fang Zhang, Michael T. Davidson, Alec B. Chaves, Scott B. Crown, Jordan M. Johnson, Dorothy H. Slentz, Paul A. Grimsrud, Deborah M. Muoio
Journal: Cell Metabolism (2023)